Putting the HIV vaccine trial news in context

We'd be remiss not to acknowledge Friday's news about positive results from an HIV vaccine trial in Thailand, a story that received tremendous attention from the print and broadcast media. (Here's more coverage from the Associated Press, Washington Post, Philadelphia Inquirer, and Reuters, and press releases from the International AIDS Vaccine Initiative and the NIH.)

The title of the NIH press release notably refers to the "modest" preventive effect of the vaccine, a clear indication that everyone ought to take a deep breath before even considering headlines about the "End of AIDS." This message evidently was received by the media (with one exception). Coverage of the trial results largely avoided the breathless optimism that often appears in stories about vaccine research against a novel target -- we've written at length on this topic. Even after Friday's news, all agree that a vaccine against HIV is, at best, many years away, and there are still prominent voices in the scientific community who doubt whether one will ever be developed.

As the stories above explain, the vaccine tested in Thailand -- a combination of two previously-unsuccessful vaccine components -- seems to have provided some additional protection against HIV infection. Experts are for now at a loss to explain the mechanism by which this could happen. The level of protection is far less than what most associate with an effective vaccine, even less than the reduced target set for a potential HIV vaccine. However, as we've documented over the years, HIV vaccine research has endured decades of setbacks and disappointments, making Friday's news a welcome departure from the norm.

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In yesterday's New York Times, Donald McNeil took a break from the H1N1 flu beat to imagine the potential implications of an AIDS vaccine. His excellent story, "If AIDS Went the Way of Smallpox," balances a look at the potential implications of a safe and effective vaccine with the reality of the limitations of the current news and the many scientific challenges that remain.

Research updates: meningococcus, dengue, and cocaine(!?!)

While we were away, there's been news on several fronts related to research on new vaccine candidates, some much farther along than others:

• Meningococcus -- The Jan. 9-16 issue of JAMA reported positive Phase II clinical trial data for a new meningococcal vaccine for infants manufactured by Novartis. The vaccine, called Menveo, would be the first available for infants, a population not covered by two meningococcal vaccines currently licensed in the U.S. Phase III trials are underway. An editorial on the results accompanied the paper in JAMA. Here's the Novartis Press Release and coverage from USA Today and HealthDay News.

• Cocaine -- There's been a great deal of attention to stories like this one on preliminary research at Baylor University that aims to develop what its (media-savvy) researchers generously describe as a "cocaine vaccine." Similar to reports of a "nicotine vaccine" that made the rounds a few years back, more interesting than speculation about a therapy that is many, many years away (if ever) is the continued broadening of the meaning of 'vaccine' by researchers working on just about any strategy that involves the immune system. Nevertheless, the media strategy worked, as one newspaper headline (originally in the Houston Chronicle) proclaims, "Researchers develop cocaine vaccine." Time magazine was on top of the story as well, publishing a news story as well as a bioethicist Q&A with the rather sweeping headline, "The Ethics of Vaccination."
  

• Dengue -- This commentary in the Jan. 9-16 issue of JAMA co-authored by NIAID Director Anthony Fauci reviews public health risks related to dengue and hemorrhagic fever in the United States. The essay reviews the progress and unanswered questions related to dengue vaccine development.
  

Roundup: Gates TB vaccine grant; NEJM paper on renewed typhoid vaccination efforts

Two items in the news recently regarding vaccines against TB and typhoid...

-- Last week, the Gates Foundation announced a $200 million, 5-year grant to the Aeras Global TB Foundation, providing renewed support for its work next-generation tuberculosis vaccines. Here are press releases from Gates and Aeras and coverage from Reuters and the Seattle Times.

-- A perspective in last week's New England Journal of Medicine (dated September 13) advocated "Putting Typhoid Vaccination on the Global Health Agenda" (subscription required for full text). The paper notes that the number of deaths attributed to typhoid are comparable or greater than those caused by cervical cancer and meningococcal meningitis, yet typhoid vaccination "has largely fallen off the international radar screen" while HPV and meningococcal vaccines receive considerable attention. The paper reviews probable causes for this development and the potential of vaccination as part of global typhoid control efforts.

HIV, Malaria, TB: vaccine research issues and planning

Several items of note over the past few weeks on research for vaccines that would have the greatest potential benefit in the developing world:

-- HIV/AIDS: In the July-August issue of Health Affairs, a paper appears titled, "The Impact of An AIDS Vaccine In Developing Countries: A New Model and Initial Results." (free abstract). Among its findings, the paper notes that a vaccine with 50% effective administered to 30% of the developing world population (both reasonable estimates) could prevent 17 million infections in 15 years.

Speaking of HIV vaccines, the death of Dr. Edward Brandt was announced this weekend. Brandt was assistant secretary of HHS in the early 1980s when AIDS and HIV were first identified. His (and HHS secretary Margaret Heckler's) overly optimistic predictions of an HIV vaccine's arrival are featured prominently in Brandt's New York Times obituary. He opined that an HIV vaccine would be available by 1987, three years after HIV was identified.

-- Malaria: A news story in the current issue of JAMA reports on malaria vaccine development ("'Roadmap' AIDS Malaria Vaccine Efforts" -- free extract.) The story provides a very good summary of progress toward a malaria vaccine and challenges needing to be addressed. The 'roadmap' referred to is the Malaria Vaccine Technology Roadmap, the product of an international series of consultations.

-- Tuberculosis: We don't talk all that often about the development of new vaccines against tuberculosis, but a paper in PLoS Medicine ("Development of New Tuberculosis Vaccines: A Global Perspective on Regulatory Issues") summarizes the content of an international meeting on the topic. The paper summarizes many of the challenges facing vaccine development and offers recommend strategies to address them.

Penn participating in study of brain cancer 'vaccine'

Over the past few years, we've been increasingly interested in the ways in which the definition of 'vaccine' has been broadened by researchers to describe a variety of new treatments that differ in form and function from vaccines of the past or present.

Tracing the evolution of the term 'vaccine' from the time of Edward Jenner to the present would be a great project for a historian or sociologist, as would attempting to understand why developers of new immunotherapies are eager to describe them as 'vaccines.' (One hypothesis -- unlikely to be palatable to critics of vaccination -- is that vaccines have a long-established record of safety and effectiveness, and classifying a new product as a 'vaccine' hopes to share in this positive connotation.)

Regardless, the latest example of this phenomenon comes from our own university, with a press release announcing, "Study Investigating Vaccine to Treat Brain Tumors Underway at Penn." As the press release and the web site of Celldex Therapeutics (the company testing the product) explain, the 'vaccine' (called CDX-110) is intended to target a particular molecule present in a significant portion of brain cancers (and other types of cancer, for that matter). The researchers' hypothesis is that administering CDX-110 to patients diagnosed with glioblastoma multiforme, the most serious form of brain cancer, will train the immune system to kill the cancer cells containing the specific target molecule.

Regardless of the branding issue, it's a very interesting and promising strategy worth following as research continues.

Legal fears block vaccine research for pregnant women, newborns

That's the topic of this story in Friday's Baltimore Sun -- "Pregnant Pause." It examines the potential for a vaccine against Group B Streptococcus -- which affects thousands of newborns annually -- and the (seemingly justifiable) reluctance of the pharmaceutical industry to pursue a vaccine against it.

Why? Among other reasons, the story points to the regulatory difficulties of testing new product in pregnant women and newborns and the extreme legal vulnerability the companies would face if allegations of safety concerns come to light (real or alleged) even after a potential vaccine was licensed.

The story goes on to outline how legal worries influence physician attitudes regarding pertussis and influenza vaccination for pregnant women, contrary to the recommendations of the scientific and medical communities. It's a very interesting story for those thinking about how science, law, and policy interact.

AP and NEJM on potential hay fever vaccine

As regular visitors are aware, we're more than a bit reluctant to join the hype over whatever the next breakthrough vaccine is said to be. As the newly licensed vaccines over the past year have shown, getting a product from the lab to the doctor's office takes a few decades and, while not necessarily a good thing, fewer than a half dozen companies are capable of guiding vaccines through the large Phase III clinical trials. So when a story appears that refers to a vaccine trial with fewer than 100 research participants for a product made by a company you've never heard of, it's a safe bet that the vaccine in question has a long road to travel.

However, we've seen that news about nicotine vaccines and the like are of interest to many. So with that disclaimer in mind, here's a story from the Associated Press (where 'dummy pills' is apparently now an acceptable synonym for 'placebo') about a vaccine in development to lessen the symptoms of hay fever. The story piggybacks on a report in this week's New England Journal of Medicine of a 25-subject clinical trial (free abstract, subscription required for full access).

Ethics of potential 'behavioral' vaccines

No newspaper headline would seem to be more relevant to our work than this one from yesterday's Chicago Tribune: "New breed of vaccines raises new ethical questions". The story in question is actually a sidebar accompanying a lengthier examination of research underway hoping, hoping, to lead to safe and effective vaccines that would target nicotine addiction, obesity, and drug addiction. Here's the opening of the larger story, "Can vaccines cure our bad habits?":

"Vaccines, the most potent medical weapon ever devised to vanquish deadly germs, are now being called on to do something totally different and culturally revolutionary--inoculate people against bad habits like overeating, cigarette smoking and drug use. Whether this new era of vaccine research can actually subdue many of the poor lifestyle choices that are today's biggest threats to health--causing obesity, cancer, heart disease and other problems--has yet to be proved."

The story is a fair account of the early-stage research underway looking at these strategies. (Back in July, the New York Times looked specifically at NicVAX, a product designed to reduce the pleasurable and addictive aspects of smoking. We wrote about that story here.)

As for the ethical issues piece, it's little more than conjecture regarding the use of products years away from arriving in doctors' offices, if ever. While it may be an interesting question to ponder whether it would be appropriate to vaccinate our children 'against' obesity, it seems that vaccines face far more pressing and immediate ethical issues on a variety of fronts that would be a much more productive use of everyone's time.

"Science Times" on nicotine vaccine in development

Yesterday's "Science Times" section of the New York Times featured a noteworthy story on research underway to develop what's being dubbed a 'vaccine against smoking.' The story, "Scientists testing vaccines to help smokers quit," looks at a nicotine vaccine (NicVAX) being developed by Nabi Biopharmaceuticals. It's the latest example of how the definition of 'vaccine' is being expanded to include a host of new directions and new targets for preventive medical interventions.

The Times story and the information available on Nabi's website (including this FAQ) explain how the vaccine is thought to work. Here's the one-paragraph summary: The vaccine will produce antibodies specific to nicotine molecules -- nicotine being the primary contributor to the pleasurable and addictive nature of smoking. In order to have these effects, nicotine must reach the brain. It is thought that the antibodies generated by the vaccine will bind to nicotine molecules inhaled by smokers. This antibody/nicotine complex will be too large to enter the brain, so that nicotine would be unable to have its usual effects. As a result, those attempting to quit smoking would be able to do so more easily, as they'd lack the typical response from smoking that makes it difficult to quit.

As with most stories previewing 'the next big thing', the availability of NicVAX is years away, and much research is needed between now and then. But it's an intriguing product and an interesting strategy, one sure to be applied to the gamut of other addictive substances if successful.

Promising data for GSK's otitis media vaccine

The CNN.com story was one of many in the past few days reporting favorably on GSK's vaccine against S. pneumoniae and H. influenza, the two leading causes of acute middle ear infections...

"The vaccine, called Streptorix, is currently being tested in ongoing Phase III clinical studies.

Researchers at the University of Defence in the Czech Republic tested the vaccine on nearly 5,000 infants and children under the age of five and said the vaccine reduced the frequency of infection by 65.5 percent.

'This study showed a statistically significant and clinically relevant reduction in episodes of acute otitis media," Dr. Roman Prymula, who headed the Phase III study, reported in the March 4 edition of Lancet.'"

The paper referenced has the catchy title "Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pnemoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study". (Lancet, 4 March 2006 (367):740-748.)

Licensure, however, is likely still a long way off: GSK plans to seek EU approval is 2007, with US approval coming at an unspecified date thereafter.